Notch信号影响耐阿霉素骨肉瘤细胞干细胞特性  

Jagged1/Notch1 signaling influences the stem cell properties in osteosarcoma cells

作　　者：梅红军 刘洋 郭卫春[2] MEI Hongjun;LIU Yang;GUO Weichun(Dept,of Orth opedics,The Fifth Hospital of Wuhan,Wuhan 430050,Hubei,China;Dept.of Orthopedics,Renmin Hospital of Wuhan University,Wuhan 430060,Hubei,China)

机构地区：[1]武汉市第五医院骨科,湖北武汉430050 [2]武汉大学人民医院骨科,湖北武汉430060

出　　处：《武汉大学学报（医学版）》2021年第4期630-633,共4页Medical Journal of Wuhan University

基　　金：武汉市科技计划项目(编号:2014062801011264)。

摘　　要：目的:探讨耐阿霉素骨肉瘤细胞干细胞特性的改变,并探究Jagged1/Notch1信号通路在其中所起的作用。方法:构建耐阿霉素骨肉瘤细胞,CCK-8实验检测细胞耐药性;Western Blot检测骨肉瘤细胞中干细胞相关基因(Oct4、Sox2、NANOG)蛋白表达水平,及Jagged1、NICD1及Notch信号通路下游靶基因Hes1等蛋白表达水平;采用悬浮克隆球实验检测细胞成球能力。结果:耐阿霉素骨肉瘤细胞干细胞相关基因(Oct4、Sox2、NANOG)蛋白表达水平上调,悬浮克隆球形成能力更强,Jagged1/Notch1信号上调;使用γ-分泌酶抑制剂DAPT下调耐药骨肉瘤细胞中Jagged1/Notch1信号通路可以导致耐药骨肉瘤细胞悬浮克隆球形成能力下降,干细胞相关基因表达下调,抑制骨肉瘤细胞干细胞特性。结论:耐阿霉素骨肉瘤细胞干细胞特性增强,可能与Jagged1/Notch1信号激活有关。Objective:To investigate the characteristics of doxorubicin-resistant osteosarcoma stem cells and its relationship with Jagged1/Notch1 signaling pathway.Methods:The doxorubicin-resistant143 B osteosarcoma cell line was constructed, and the chemoresistance was validated by CCK-8 assay.Western Blot was used to detect the expression level of the stem cell-related genes(Oct4, Sox2,and NANOG) and Notch signaling pathway related genes(Jagged1, NICD1, and Hes1).Cell formation ability was detected by the formation assay of spheres.Results:The expression level of the stem cell-related genes(Oct4, Sox2, and NANOG) were increased in doxorubicin-resistant osteosarcoma cells.The cell formation ability was increased in doxorubicin-resistant osteosarcoma cells.The Jagged1/Notch signaling pathway was activated in doxorubicin-resistant osteosarcoma cells.Downregulating the Jagged1/Notch1 signaling pathway by γ-secretase inhibitor DAPT reversed the enhancement of stem cell properties in doxorubicin-resistant osteosarcoma cells.Conclusion:The stem cell properties are enhanced in doxorubicin-resistant osteosarcoma cells, which are related to the activation of Jagged1/Notch1 signaling pathway.

关 键 词：骨肉瘤 阿霉素 Jagged1/Notch1信号通路 干细胞特性 

分 类 号：R738.1[医药卫生—肿瘤]